In the proposed studies, we will examine the causes of the pulmonary edema and pulmonary insufficiency after acute pancreatitis in the sheep lung lymph fistula preparation. First, the effects (both short-term and long-term) of acute pancreatitis on lung fluid and protein exchange, pulmonary hemodynamics and gas exchange will be characterized. Then studies will examine whether the pulmonary edema is due to increased pulmonary microvascular pressure or increase in lung endothelial permeability to proteins. This will be attempted by analyzing the changes in lung fluid and protein after small increases in left atrial pressure and by studying the alterations in the selectivity of the endothelial barrier to endogenous proteins. The third series of studies will determine whether the pulmonary vascular changes, edema and gas exchange impairment are due to the release of humoral factors into the central circulation, whether via the systemic lymphatics, venous circulation or both. The final studies will examine the role of the putative factors implicated in the pathogenesis of pulmonary edema after acute pancreatitis; that is, fibrin entrapment and sequestration of platelets and granulocytes in the lung, complement activation, activation of kallikrein-kinin system, release of proteolytic enzymes, release of lipase and phospholipase A2 and resulting generation of free fatty acids and lysolecithin, and the release of histamine.